Lactation in the rat is characterized by an inibition of ovarian cyclicity which correlates with a suppression of gonadotropin secretion. Studies are aimed at delineating the mechanisms by which the suckling stimulus and the increase in prolactin which follows suckling inhibit pituitary gonadotropin secretion. The proposed experiments will attempt to establish that GnRH release from the hypthalamus is decreased during lactation and that the deficit in GnRH release accounts for the decrease in pituitary GnRH receptors and pituitary responsiveness to GnRH and for the absence of pulsatile LH secretion. Studies will also examine the recovery process for gonadotropin secretion following removal of the suckling stimulus in an attempt to gain insight into basic mechanisms regulating pulsatile GnRH secretion and GnRH regulation of gonadotropin secretion. The control of pituitary gonadotropin secretion will be studied by examining the period after removal of the suppressive suckling stimulus when gonadotropin secretion returns to normal. The following parameters will be assessed: the increase in pituitary GnRH receptor content, the increase in pituitary responsiveness to GnRH, and an analysis of endogenous LH pulse amplitudes and LH interpulse intervals. Lactating rats will be exposed to a physiological pulsatile GnRH replacement regimen to determine whether pulsatile LH secretion can be restored to normal in the continued presence of the suckling stimulus. To quantify GnRH secretion from the hypothalamus during lactation, in vitro perifusion of hypothalamic fragments will be performed. GnRH release rates will be determined during the estrous cycle, lactation and the recovery phase after pup removal. Norepinephrine, serotonin and dopamine activity also will be assessed during these states by measuring monoamine activity in specific brain areas using liquid chromatography with electrochemical detection. Experiments are aimed at determining whether increases in serotonergic or opioidergic activity play a role in suckling-induced decreases in gonadotropin secretion. Also, the mechanisms by which progresterone suppresses pulsatile GnRH secretion will be examined. These proposed studies should provide insight into the mechanisms underlying normal cyclic function, and by identifying factors which suppress cyclicity may contribute to new approaches for contraception.